What is a suitable substitute for Perampanel (perampanel) in case of neurological adverse effects?

Substitute for Perampanel in Case of Neurological Adverse Effects

Levetiracetam is the preferred substitute for perampanel when neurological adverse effects occur, as it is the first-line antiepileptic drug at most neuro-oncology centers with overall good tolerability, though psychiatric side effects remain a concern in some patients. 1

Primary Recommendation: Levetiracetam

• Levetiracetam has become the drug of first choice at most neuro-oncology centers due to its efficacy and overall good tolerability profile 1
• The EANO-ESMO guidelines specifically recommend levetiracetam and lamotrigine as preferred first-choice options because of their efficacy and overall good tolerability 1
• Levetiracetam is particularly advantageous as it is a non-enzyme-inducing antiepileptic drug, avoiding interactions with chemotherapy, targeted therapies, and steroids 1

Alternative Option: Lamotrigine

• Lamotrigine is an equally preferred first-line alternative with good antiseizure activity and favorable tolerability 1
• The main limitation is that lamotrigine requires a period of several weeks until sufficient drug levels are reached, making it less suitable for urgent substitution 1
• Lamotrigine demonstrated no serious adverse effects in safety studies, with only mild transient nausea reported in some patients 1

Additional Considerations

Lacosamide as Add-On Therapy

• Lacosamide may assume a larger role as an add-on treatment for patients whose seizure disorder is not controlled by monotherapy 1
• The tolerability profile of IV lacosamide is consistent with oral lacosamide, with adverse effects being mild or moderate (dizziness, headache, somnolence) 1

Valproic Acid in Select Cases

• Valproic acid still has a firm place in some centers given its efficacy and overall good tolerability 1
• Critical contraindication: Valproic acid must not be used in females who may become pregnant 1
• Drug interactions need to be checked on a regular basis 1

Common Pitfalls to Avoid

Drugs to Avoid

• Phenytoin, phenobarbital, and carbamazepine are no longer recommended as agents of first choice due to their side-effect profile and drug interactions, especially with steroids and various cytotoxic and targeted agents 1
• Enzyme-inducing anticonvulsants should be avoided in patients with brain tumors 1

Context of Perampanel's Neurological Side Effects

• Perampanel commonly causes CNS-related adverse events including dizziness, somnolence, fatigue, and irritability, which are dose-related 2, 3
• Psychiatric disorders, instability, and irritability are frequent side effects that sometimes require dose reduction or discontinuation 4
• The 12 mg dose of perampanel has significantly higher withdrawal rates due to adverse events compared to lower doses 3

Practical Algorithm for Substitution

1. Discontinue or taper perampanel based on severity of neurological adverse effects
2. Initiate levetiracetam immediately if rapid seizure control is needed, as it can be loaded and achieves therapeutic levels quickly 1
3. Consider lamotrigine if time permits for gradual titration and patient has no urgent seizure control needs 1
4. Monitor for psychiatric side effects with levetiracetam (irritability, mood changes), which occur in some patients 1
5. Add lacosamide if monotherapy with levetiracetam or lamotrigine proves insufficient 1